Effects of Oral Morphine on Dyspnea in Patients with Cancer: Response Rate, Predictive Factors, and Clinically Meaningful Change (CJLSG1101)

Abstract

Background Although the efficacy of parenteral morphine for alleviating dyspnea has been previously demonstrated in several studies, little is known regarding the efficacy of oral morphine for dyspnea among patients with cancer, including its response rate and predictive factors of effectiveness. Therefore, the aim of this study was to clarify the effectiveness of oral morphine on dyspnea in patients with cancer and elucidate the predictive factors of its effectiveness. Subjects, Materials, and Methods In this multicenter prospective observational study, we investigated the change in dyspnea intensity in patients with cancer before and after the administration of oral morphine by using a visual analog scale (VAS). We also administered a self‐assessment questionnaire to determine whether the patients believed oral morphine was effective. Results Eighty patients were enrolled in the study, and 71 of these patients were eligible. The least square mean of the VAS scores for dyspnea intensity was 53.5 at baseline, which decreased significantly to 44.7, 40.8, and 35.0 at 30, 60, and 120 minutes after morphine administration, respectively. Fifty‐four patients (76.1%) reported that oral morphine was effective on the self‐assessment questionnaire. Among the background factors, a high score for “sense of discomfort” on the Cancer Dyspnea Scale (CDS) and a smoking history of fewer pack‐years were associated with greater effectiveness. Conclusion Oral morphine was effective and feasible for treating cancer‐related dyspnea. A higher score for “sense of discomfort” on the CDS and a smaller cumulative amount of smoking may be predictive factors of the effectiveness of oral morphine. Implications for Practice This study demonstrated that oral morphine was effective in alleviating cancer‐related dyspnea due to multiple factors including primary lung lesions, airway narrowing, and pleural effusion. Approximately 76% of patients reported that oral morphine was effective. A higher score for “sense of discomfort” on the Cancer Dyspnea Scale and a lower cumulative amount of smoking may be predictive factors for the effectiveness of oral morphine. Interestingly, respiratory rates in patients who reported the morphine to be effective decreased significantly after oral morphine administration, unlike the respiratory rates in “morphine‐ineffective” patients.

Physician-Perceived Predictive Factors for the Effectiveness of Drugs for Treating Cancer Dyspnea: Results of a Nationwide Survey of Japanese Palliative Care Physicians

“…1,6 In addition, other effects of opioids may influence these results, that is, a possible reduction of respiratory rate improving tachypnea or respiratory effort, and an antitussive effect against dry cough. [16][17][18] However, a previous study has shown that opioid treatment neither causes a decrease in respiratory rate nor the effectiveness of opioids for treating patients with tachypnea. 19 Good PS may be selected for because dyspnea worsens in the terminal phase, when PS also declines.…”

“…As no preexisting questionnaires matched our specific requirements, we developed a novel ad hoc questionnaire based on a literature review and discussion among the investigators. 1,2,[8][9][10][11][12][13][14][15][16] We described a hypothetical scenario of an adult ambulatory cancer patient with an expected survival of more than several months and a dyspnea score of 2 or 3 on the modified Medical Research Council Scale. For this hypothetical case, we inquired about the physician-perceived predictive factors for the effectiveness of drugs (opioids, benzodiazepines, and corticosteroids) in treating cancer dyspnea.…”

Experience of symptom control, anxiety and associating factors in a palliative care unit evaluated with Support Team Assessment Schedule Japanese version

“…Although STAS is not a subjective patient-reported outcome scale, its usefulness should be emphasized when considering the condition of patients in palliative care settings who might be delirious or in a drowsy state. Regarding the observation period required for symptom control, although effects of opioids against dyspnea can be evaluated within some hours to 2 days 40 , 41 , 14 days are necessary for opioid rotation against cancer pain treatment 42 . A 2-week period is also applied in some studies evaluating transitional changes of anxiety 43 , 44 .…”

Multidimensional measurement of breathlessness: recent advances

“…Clinically these instruments have been used to describe breathlessness severity as a characteristic of cohorts (CDS [35]), differences between groups (D-12: frailty classifications in people with COPD [37]) and to identify changes in breathless sensation over time (D-12: across 3 months following admission to hospital for acute exacerbation of COPD with greater changes at each time point for physical subdomains (sensory qualities) versus affective subdomains [25 && ]). There are an increasing number of studies including multidimensional instruments to assess the impact of interventions on the sensation of breathlessness (MDP: before and 1 month after initiation of noninvasive ventilation in people living with ALS with chronic respiratory failure [33 && ]; pulmonary rehabilitation with and without inspiratory muscle training in people with severe/very severe COPD [38]; D-12: cognitive behavioural therapy for people with severe asthma and anxiety/ depression [30 && ]; CDS: oral morphine for cancerrelated breathlessness [39]).…”

“…Pulm HT [31] ILD [32] Lung cancer [34] Y Y English [16], French [28], Portuguese [26], Italian [27], Swedish [36] Cancer Dyspnoea Scale [18] Y Y Y 1 2 Ordinal 1-5 Advanced lung cancer [18] Advanced lung cancer [22,23] Advanced cancer [21,35,39] Y Y Japanese [18], English [18], Swedish [23], Vietnamese [22], Hindi [21], Marathi [21] Dyspnea-ALS-scale Asthma, CF, healthy (8-18 years) [58] Histamine challenge [59] Exertional dyspnoea ( Dyspnoea-12 [16] Multidimensional Dyspnea Profile [17] Cancer Dyspnea scale (CDS) [18] Dyspnea-ALSscale [14] a None (0) Mild ( 1 sensations assessed by the MDP have been reported to be similar between aerosolized furosemide and saline [41…”